In the first 3 year phase of this research we will define the effects of STLV-III/Delta infection in rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) monkeys since our preliminary evidence indicate both species may be susceptible to opportunistic infections and/or lymphomas associated with STLV-III infection. Information on the susceptibility of cynomolgus monkeys could be important during the testing phase of this project when large numbers of animals may be required. We will determine the effects of STLV-III/Delta infection on the host immune system by in vitro studies of lymphocyte functions and in vivo studies of lymphocyte subsets. We will investigate whether pathologic cellular or humoral immunologic responses occur which may augment the destruction of STLV-III infected OKT4+ lymphocytes. The effects of STLV-III infection on the susceptibility to opportunistic infections with rhesus cytomegalovirus and rhesus EBV-related viruses, which have occurred frequently in STLV-III infected monkeys in our preliminary studies, will be determined. STLV-III/Delta DNA will be cloned and mapped by restriction endonuclease digestion. Genetic comparisons of STLV-III isolated from different species and locations will be performed. Nucleotide sequences will be compared to define regions of genetic conservation and variability. STLV-III proteins will be identified, characterized and purified. Peptide maps of different isolates will be compared to examine protein variability. Purified proteins will be used as antigens for in vitro studies of cell-mediated immunity. STLV-III proteins will be quantitated in clinical materials using a sandwich enzyme-linked immunoassay (virus capture assay). Challenge systems involving the reduced resistance of STLV-III infected monkeys to experimental opportunistic infections or decreased ability to respond to antigenic challenge will be explored. In the second two-year phase of this contract we will use the STLV-III infection model for testing the effectiveness of antiretrovirus drugs and/or vaccines. The effects of STLV-III infection with and without antiviral treatment or prior to vaccination will be compared using criteria established during the first phase of the project.